Class I Genes of the Major Histocompatibility Complex: Structural Studies on Genes of the Tla Locus

Year: 1986 DOI: 10.7907/ymba-8s86
This thesis contains investigations into the structure of molecules encoded within the mouse major histocompatibility complex. The first chapter [Steinmetz, M., J. G. Frelinger, D. Fisher, T. Hunkapiller, D. Pereira, S. M. Weissman, S. G. Nathenson, and L. Hood, Cell 24: 125] describes the isolation and characterization of the first cDNA clones encoding murine transplantation (H-2) antigens. This study showed that H-2 antigens contain DNA and protein sequences related to immunoglobulin (Ig) molecules, but that the similarity does not include the great somatic diversity characteristic of Ig molecules.

The second chapter contains methods for cloning and sequencing in M13 bacteriophage vectors. Included is a novel method of generating overlapping subclones for DNA sequencing by making a family of deletions in a DNA insert cloned in M13.

In the third chapter [Fisher, D. A., S. W. Hunt, and L. Hood J. Exp. Med. 162: 528], the complete structure of a gene encoding a serologically defined thymus leukemia (TL) antigen is elucidated. TL antigen is encoded in a gene, gene Tl3c, closely related to H-2 antigens, and appears to have undergone a gene conversion event with an H-2 gene. Tla-specific probes subcloned from T13C enabled us to examine the organization of the eighteen cross hybridizing class I genes of the Tla region.

The last chapter contains the sequence of another gene, gene T1C, previously identified as encoding TL antigen. However, the T1C gene is a non-functional pseudogene, and was probably mis-identified. There is an apparent site of recombination in the T1C gene that occurs precisely at a B2 Alu repeat sequence.